CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations.
CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations.
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DOI：
10.1186/s40478-020-01084-4
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发表时间：
2020-11-25
影响因子：
7.1
通讯作者：
Nishino I
中科院分区：
文献类型：
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作者：
Ogasawara M;Iida A;Kumutpongpanich T;Ozaki A;Oya Y;Konishi H;Nakamura A;Abe R;Takai H;Hanajima R;Doi H;Tanaka F;Nakamura H;Nonaka I;Wang Z;Hayashi S;Noguchi S;Nishino I
眼咽远端肌病是一种罕见的遗传性肌肉疾病，其特征是进行性肢体远端无力、上睑下垂、眼肌麻痹、球肌无力和肌肉活检中出现边缘空泡。最近，LRP12和GIPC1两个基因非编码区CGG重复序列的扩展被报道与OPDM的发病有关。此外，最近有报道称，NOTCH2NLC的CGG重复扩增导致了神经元核内包涵体疾病(NIID)。我们的目的是确定在NOTCH2NLC(OPDM_NOTCH2NLC)中有CGG重复扩张的OPDM患者的临床病理特征。注意到来自201个家系的211名临床或临床病理诊断为OPDM或眼咽肌营养不良的患者，采用重复引物-聚合酶链式反应(Repeat Primed-PCR)筛查NOTCH2NLC中CGG扩张。对确诊的OPDMNOTCH2NLC患者的临床资料和肌肉病理切片进行了复习。用免疫组织化学和电子显微镜(EM)检测肌核内包涵体。7例日本OPDM患者在NOTCH2NLC中有CGG重复扩张。所有7例患者临床上均表现为上睑下垂、眼肌麻痹、构音障碍和肌肉无力；肌肉病理检查显示肌核内包涵体，除边缘空泡外，还染色有抗多聚泛素蛋白、抗SUMO1和抗p62抗体，这些抗体可诊断为NIID(典型的皮肤活检)。EM标本仅取自1例，核内包裹体直径为12.6 ± 1.6 nm。我们确定了7名OPDM_NOTCH2NLC患者。我们的患者有各种额外的中枢和/或外周神经系统受累，尽管所有患者的临床病理都是相容的；因此，他们被诊断为患有OPDM，并在NOTCH2NLC中扩展了由CGG重复扩张引起的神经肌肉退行性疾病的表型。
Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive distal limb weakness, ptosis, ophthalmoplegia, bulbar muscle weakness and rimmed vacuoles on muscle biopsy. Recently, CGG repeat expansions in the noncoding regions of two genes, LRP12 and GIPC1, have been reported to be causative for OPDM. Furthermore, neuronal intranuclear inclusion disease (NIID) has been recently reported to be caused by CGG repeat expansions in NOTCH2NLC. We aimed to identify and to clinicopathologically characterize patients with OPDM who have CGG repeat expansions in NOTCH2NLC (OPDM_NOTCH2NLC). Note that 211 patients from 201 families, who were clinically or clinicopathologically diagnosed with OPDM or oculopharyngeal muscular dystrophy, were screened for CGG expansions in NOTCH2NLC by repeat primed-PCR. Clinical information and muscle pathology slides of identified patients with OPDM_NOTCH2NLC were re-reviewed. Intra-myonuclear inclusions were evaluated using immunohistochemistry and electron microscopy (EM). Seven Japanese OPDM patients had CGG repeat expansions in NOTCH2NLC. All seven patients clinically demonstrated ptosis, ophthalmoplegia, dysarthria and muscle weakness; they myopathologically had intra-myonuclear inclusions stained with anti-poly-ubiquitinated proteins, anti-SUMO1 and anti-p62 antibodies, which were diagnostic of NIID (typically on skin biopsy), in addition to rimmed vacuoles. The sample for EM was available only from one patient, which demonstrated intranuclear inclusions of 12.6 ± 1.6 nm in diameter. We identified seven patients with OPDM_NOTCH2NLC. Our patients had various additional central and/or peripheral nervous system involvement, although all were clinicopathologically compatible; thus, they were diagnosed as having OPDM and expanding a phenotype of the neuromyodegenerative disease caused by CGG repeat expansions in NOTCH2NLC.
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影响因子：
3.7
作者：
Zhao J;Liu J;Xiao J;Du J;Que C;Shi X;Liang W;Sun W;Zhang W;Lv H;Yuan Y;Wang Z
通讯作者：
Wang Z
影响因子：
--
作者：
SATOYOSHI, E;KINOSHITA, M
通讯作者：
KINOSHITA, M
影响因子：
9.9
作者：
Sone, J.;Tanaka, F.;Sobue, G.
通讯作者：
Sobue, G.
人类特异性 NOTCH2NLC 基因中 GGC 重复序列的扩展与特发性震颤相关。
影响因子：
14.5
作者：
Sun, Qi-Ying;Xu, Qian;Tang, Bei-Sha
通讯作者：
Tang, Bei-Sha
影响因子：
9.9
作者：
Durmus, H.;Laval, S. H.;Serdaroglu-Oflazer, P.
通讯作者：
Serdaroglu-Oflazer, P.